Poster Presentation The International Congress of Neuroendocrinology 2014

Disruptions in the Oxt system contribute to altered sensorimotor gating (#259)

Megan Rich
, Heather Caldwell

One endophenotype of schizophrenia is a lack of sensorimotor
gating. Across cross species, sensorimotor gating can be measured using
prepulse inhibition (PPI) of the acoustic startle reflex. PPI is regulated by
the cortico-striato-pallido-pontine (CSPP) circuit, thus, damage to this
circuit results in impaired PPI. We have previously reported that compared to
controls, oxytocin knockout (Oxt −/−) mice have larger deficits in PPI
following administration of the NMDA receptor antagonist, phencyclidine (PCP). This
suggests that endogenous oxytocin (Oxt) may protect against the PPI-disrupting
effects of PCP. These effects do not
appear to be regulated by the Oxt receptor (Oxtr), as Oxtr knockout (Oxtr −/−)
mice treated with PCP look similar to controls. To confirm that PCP-induced PPI
deficits in Oxt −/− mice are due to the absence of Oxt, we attempted to rescue
PPI in Oxt −/− mice by intracerebroventricularly administering Oxt prior to
treatment with PCP. We also quantified NMDA expression within the CSPP circuit
in Oxt −/− mice, Oxtr −/− mice, and controls, since glutamate signaling is
important to the functioning of the CSPP circuitry. We found that pretreatment
with Oxt was able to partially rescue PCP-induced disruptions of PPI in Oxt −/−
mice. We also found that NMDAR1 are downregulated in the amygdala of Oxt −/−
mice, but not in Oxtr −/− mice. Our preliminary data also suggest that there
are no differences in the expression of NMDR2A and NMDR2B between the
aforementioned groups. Taken together, these data continue to support the
hypothesis that disruptions in Oxt signaling, and Oxt interactions with the
glutamate system, may contribute to altered sensorimotor gating. Since there is
evidence of Oxt dysregulation in schizophrenic patients, which may contribute
to altered sensorimotor gating, our findings provide a mechanism through which
the Oxt system may interact with the CSPP circuitry.